Interactions Between Kisspeptins and Neurokinin B - Kisspeptin Signaling in Reproductive Biology - page 330

restraint on the hypothalamic expression of Kiss1 /kisspeptins in pubertal animals,
which can be reverted by exogenous kisspeptin [ 117 ]. Given the fact that the NKB/
NK3R system is also present in the metabolic conveyor that KNDy neurons in the
ARC constitute, it was reasonable to assume that the action of NKB is also subjected
to metabolic regulation during (and after) puberty. In this sense, a recent study docu-
mented the sensitivity of this system to metabolic cues [ 118 ]. In more detail, a later
study in pubertal female rats demonstrates a signifi cant suppression of Tacr3 , and to
a lesser extent Tac2 , in the ARC after 48-h fasting [ 40 ], replicating the previously
described expression profi le of Kiss1 in both the ARC and AVPV [ 117 ]. Moreover,
in this study, LH responses to senktide administration in pubertal (36-d) rats are not
only preserved but even augmented in fasting conditions, suggesting a possible sen-
sitization of its stimulatory effects under conditions of negative energy balance—
again, resembling previous fi ndings on the gonadotropin-releasing actions of
kisspeptins [ 117 , 119 ]. Additionally, chronic administration of senktide to prepuber-
tal female rats subjected to caloric restriction was suffi cient to partially rescue mark-
ers of puberty onset, e.g., vaginal opening and LH secretion [ 40 ], as previously
reported for kisspeptin [ 117 ]. On the other hand, situations of exceedingly high
caloric intake, such as rats subjected to high fat diet prepubertally, exhibited preco-
cious puberty that correlates with the advancement in the timing of Kiss1 and Tac2
expression that, in turn, was associated with the advancement in LH pulsatility [ 120 ].
Altogether, the above observations suggest that the NKB system is subjected to
modulation by metabolic cues, at least during pubertal progression, probably facili-
tating the transmission of the energy status of the organism on to the Kiss1 system,
most likely, at the level of the ARC. However, kisspeptin-independent pathways for
the stimulatory effects of NKB on the gonadotropic axis at puberty cannot be
excluded—which remains to be explored. Noteworthy, recent studies associate
KNDy neurons in the ARC with the regulatory (inhibition) effect that estrogens
exert on body weight [ 66 ]. This fi nding poses the KNDy neuron as a nodal regula-
tory center for the integration of reproductive axis and energy balance; however, the
mechanisms underlying this effect need to be deciphered.
Conclusion and Future Perspectives
Our knowledge of the neuronal interactions that potentially impinge the accurate
functioning of the endocrine system is rapidly evolving. Particularly, in recent years,
reproductive neuroendocrinologists are witnessing the appearance of a constellation
of central factors that signifi cantly contribute to the modulation of GnRH release. In
this context, since 2003, the scientifi c community has enthusiastically welcomed
Kiss1 neurons as key elements to answer remaining open questions in the physiol-
ogy of GnRH release. More recently, the NKB system has added a new level of
complexity to Kiss1 neurons. Compelling evidence suggests that NKB plays a criti-
cal role in the control of kisspeptin release, at least at the level of the ARC. Not only
is NKB able to modulate gonadotropin release through, according to recent studies,